tbuckley/cabot-search huggingface dataset:
First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS) (NCT02893332).
Authors: Xiaoshan Wang, Ming Zeng
Journal: Journal of Clinical Oncology (2020)

9508 Background: The effectiveness of aggressive local therapy for oligometastatic non-small-cell lung cancer (NSCLC) is unknown. This multi-institutional, randomized, open label, phase III clinical trial was performed to assess upfront stereotactic radiotherapy to all sites at diagnoses in previously untreated EGFRm oligometastatic non-small-cell lung cancer on progression-free survival and overall survival. Methods: The study was conducted at five centers located in different provinces of China.Eligible participants had pathologically confirmed adenocarcinoma, gene sequencing confirmed EGFRm, stage IV, five or fewer metastatic disease lesions, an ECOG performance status score of ≤ 2, systemic therapy naive, and no brain disease before randomization.Participants were randomized to receive either first-line tyrosine kinase inhibitor (TKI) treatment alone or up front stereotactic radiotherapy to all sites of disease along with TKI treatment.The primary endpoint was progression-free survival and the secondary endpoint was overall survival. Results: From January 2016 to January 2019, 133 participants were enrolled, including 65 (48.8%) in the TKI arm who received standard of care TKI alone and 68 (51.1%) in the stereotactic radiotherapy sites at diagnosis arm who received stereotactic radiotherapy and TKI.At a median follow-up of 19.6 months (IQR 9.4 - 41.0), the median progression-free survival for tyrosine kinase inhibitor alone was 12.5 months, and for tyrosine kinase inhibitor and stereotactic radiotherapy was 20.20months, respectively (HR 0.6188 [95% CI 0.3949-0.9697], log rank P&lt; .001). The median overall survival in the TKI alone arm was 17.40 months, and for TKI and stereotactic radiotherapy arm was 25.50 months, respectively (HR 0.6824 [95% CI 0. 4654-1.001], log rank P&lt; .001). Adverse events were similar between groups, with no grade 5 or deaths due to treatment. Grade 3/4 adverse events with or without radiotherapy included pneumonitis (7.3% vs. 2.9%; P&gt; .05) and esophagitis (4.4%vs. 3.0% P&gt; .05). Conclusions: Upfront stereotactic radiotherapy to sites at diagnosis along with first line TKI improved both progression-free survival and overall survival significantly compared with TKI alone. This finding suggests aggressive local therapy to sites at diagnosis should be explored further in large cohort phase III trials as a standard treatment option in this clinical scenario. Clinical trial information: NCT02893332 .
Gestational Diabetes Mellitus
Authors: Siri L. Kjos, Thomas A. Buchanan
Journal: New England Journal of Medicine (1999)

Gestational diabetes mellitus is defined as glucose intolerance that is first detected during pregnancy.1 This simple definition belies the complexity of a condition that spans a spectrum of glycemia, pathophysiology, and clinical effects and for which there is a wide diversity of opinion regarding detection and clinical management. There is convincing evidence that mild maternal hyperglycemia is a risk factor for fetal morbidity,2 but that morbidity occurs only in a minority of cases. Failure to recognize and treat the condition will result in unnecessary morbidity in some pregnancies, whereas overly aggressive approaches to detection and treatment will result in unneeded . . .
Improving Protection for Research Subjects
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2002)

In March 1996, Hoiyan Wan, a 19-year-old nursing student and a healthy volunteer in a study at the University of Rochester, died two days after undergoing bronchoscopy as part of the study. During the procedure, she received a fatal dose of lidocaine. A report that followed a state investigation criticized the researchers, the institutional review board (IRB), and the university.1 Wan's death led to many changes at the University of Rochester, including the establishment of training programs for investigators and an overhaul and expansion of the university's IRBs. The university's response is sometimes cited as a model for other institutions . . .
Inappropriate Secretion of Thyroid-Stimulating Hormone
Authors: BRUCE D. WEINTRAUB
Journal: Annals of Internal Medicine (1981)

Recent studies have provided major new insights into the syndromes of inappropriate secretion of thyroid-stimulating hormone (TSH), a heterogeneous group of disorders in which patients show inappropriately elevated levels of serum immunoactive TSH in the presence of elevated free thyroid hormone levels. Certain of these patients appear to have a non-neoplastic disorder associated with variable degrees of pituitary and peripheral resistance to the action of thyroid hormone, whereas others harbor a tumor of pituitary thyrotropic cells. Measurement of free serum α subunit has proved valuable in differentiating these disorders, showing normal α concentration and α-to-TSH ratios in the non-neoplastic and highly elevated values in the neoplastic disorders. All these syndromes appear unrelated to Graves' disease because thyroid-binding and thyroid-stimulating antibodies are usually absent. Some of these patients also have abnormal metabolism of thyroid hormones. Although the pathogenesis of these syndromes remains to be elucidated, increased recognition and study of these patients should provide fundamental insights into the regulation of TSH secretion as well as the action of thyroid hormone.
Role of Dynamic Contrast-Enhanced Magnetic Resonance (MR) Imaging and Proton MR Spectroscopic Imaging in the Detection of Local Recurrence after Radical Prostatectomy for Prostate Cancer
Authors: Alessandro Sciarra, Valeria Panebianco, Stefano Salciccia, Marcello Osimani, Danilo Lisi, Mauro Ciccariello, Roberto Passariello, Franco Di Silverio, Vincenzo Gentile
Journal: European Urology (2008)
Association Between Performance Measures and Clinical Outcomes for Patients Hospitalized With Heart Failure
Authors: Gregg C. Fonarow, William T. Abraham, Nancy M. Albert, Wendy Gattis Stough, Mihai Gheorghiade, Barry H. Greenberg, Christopher M. O’Connor, Karen Pieper, Jie Lena Sun, Clyde Yancy, James B. Young, for the OPTIMIZE-HF Investigators and Hospitals
Journal: JAMA (2007)
Evaluation of Guideline Recommendations on Oral Medications for Type 2 Diabetes Mellitus
Authors: Wendy L. Bennett, Olaide A. Odelola, Lisa M. Wilson, Shari Bolen, Saranya Selvaraj, Karen A. Robinson, Eric B. Bass, Milo A. Puhan
Journal: Annals of Internal Medicine (2012)

Background: Clinical practice guidelines have an important role in guiding choices among the numerous medications available to treat type 2 diabetes mellitus, but little is known about their quality. Purpose: To assess whether guidelines on oral medications for type 2 diabetes are consistent with a systematic review of the current evidence and whether the consistency of the guidelines depends on the quality of guideline development. Data Sources: MEDLINE, CINAHL, and guideline-specific databases were searched between July 2007 and August 2011, after the 2007 publication of a peer-reviewed systematic review on oral diabetes medications. Study Selection: Two reviewers independently screened citations to identify English-language guidelines on oral medications to treat type 2 diabetes that were applied in the United States, United Kingdom, and Canada. Data Extraction: Reviewers assessed whether the guidelines addressed and agreed with 7 evidence-based conclusions from the 2007 systematic review. Two reviewers independently rated guideline quality by using 2 domains from the Appraisal of Guidelines Research and Evaluation instrument. Data Synthesis: Of the 1000 screened citations, 11 guidelines met the inclusion criteria. Seven guidelines agreed with the conclusion that metformin is favored as the first-line agent. Ten guidelines agreed that thiazolidinediones are associated with higher rates of edema and congestive heart failure compared with other oral medications to treat type 2 diabetes. One guideline addressed no evidence-based conclusions, and 5 guidelines agreed with all 7 conclusions. The summary scores of the rigor of development (median, 28.6% [range, 16.7% to 100.0%]) and editorial independence (median, 75.0% [range, 8.3% to 100.0%]) domains varied greatly across guidelines. Guidelines that received higher quality scores contained more recommendations that were consistent with the evidence-based conclusions. Limitation: Only English-language guidelines targeting users in the United States, United Kingdom, and Canada that contained recommendations on oral medications were included. Conclusion: Not all practice guidelines on oral treatment of type 2 diabetes were consistent with available evidence from a systematic review. Guidelines judged to be of higher quality contained more recommendations consistent with evidence-based conclusions. The quality of guideline development processes varied substantially. Primary Funding Source: Agency for Healthcare Research and Quality.
Postoperative Infections Traced to Contamination of an Intravenous Anesthetic, Propofol
Authors: Siiri N. Bennett, Michael M. McNeil, Lee A. Bland, Matthew J. Arduino, M. Elsa Villarino, Dennis M. Perrotta, Dale R. Burwen, Sharon F. Welbel, David A. Pegues, Leonardo Stroud, Paul S. Zeitz, William R. Jarvis
Journal: New England Journal of Medicine (1995)

Between June 1990 and February 1993, the Centers for Disease Control and Prevention conducted investigations at seven hospitals because of unusual outbreaks of bloodstream infections, surgical-site infections, and acute febrile episodes after surgical procedures.
Circadian Timekeeping in Health and Disease
Authors: Martin C. Moore-Ede, Charles A. Czeisler, Gary S. Richardson
Journal: New England Journal of Medicine (1983)

Part 1 of this review outlined recent advances in characterizing the properties of hypothalamic circadian pacemakers. In Part 2 we describe the implications of this rhythmicity for clinical medicine.Circadian Rhythms in Medical DiagnosisAlmost every physiologic variable that is used as a diagnostic indicator has been shown to exhibit a circadian rhythm.3 One consequence of this has been the gradual alteration of the common perception that physiologic variables are tightly regulated to a fixed set point and that any movement away from this value is equivalent to disease. Such an oversimplification of the concept of homeostasis must be modified . . .
Non-Hodgkin’s Lymphomas, Version 3.2012
Authors: Andrew D. Zelenetz, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, Naresh Bellam, John C. Byrd, Myron S. Czuczman, Luis Fayad, Martha J. Glenn, Jon P. Gockerman, Leo I. Gordon, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Barbara Pro, Nishitha Reddy, Lubomir Sokol, Lode Swinnen, Christina Tsien, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Maoko Naganuma, Mary A. Dwyer
Journal: Journal of the National Comprehensive Cancer Network (2012)

These NCCN Guidelines Insights summarize several key updates to the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas (NHL) and describe the clinical evidence supporting the updates. The featured updates include changes to the recommendations for treatment options in patients with chronic lymphocytic leukemia (including in elderly or frail patients and patients with poor-risk cytogenetics), guidance surrounding surveillance imaging for follow-up of patients with NHL, and the addition of first-line consolidation options for patients with mantle cell lymphoma.
Cellular therapy in periodontal regeneration
Authors: Javier Nuñez, Fabio Vignoletti, Raul G. Caffesse, Mariano Sanz
Journal: Periodontology 2000 (2019)

Abstract Periodontitis is a chronic inflammatory condition leading to destruction of the tooth supporting tissues, which if left untreated may cause tooth loss. The treatment of periodontitis mainly aims to arrest the inflammatory process by infection control measures, although in some specific lesions a limited periodontal regeneration can also be attained. Current regenerative approaches are aimed to guide the cells with regenerative capacity to repopulate the lesion and promote new cementum and new connective tissue attachment. The first phase in periodontal tissue regeneration involves the differentiation of mesenchymal cells into cementoblasts to promote new cementum, thus facilitating the attachment of new periodontal ligament fibers to the root and the alveolar bone. Current regenerative approaches limit themselves to the confines of the lesion by promoting the self‐regenerative potential of periodontal tissues. With the advent of bioengineered therapies, several studies have investigated the potential use of cell therapies, mainly the use of undifferentiated mesenchymal cells combined with different scaffolds. The understanding of the origin and differentiation patterns of these cells is, therefore, important to elucidate their potential therapeutic use and their comparative efficacy with current technologies. This paper aims to review the in vitro and experimental studies using cell therapies based on application of cementoblasts and mesenchymal stem cells isolated from oral tissues when combined with different scaffolds.
Mortality among Patients Admitted to Hospitals on Weekends as Compared with Weekdays
Authors: Chaim M. Bell, Donald A. Redelmeier
Journal: New England Journal of Medicine (2001)

The level of staffing in hospitals is often lower on weekends than on weekdays, despite a presumably consistent day-to-day burden of disease. It is uncertain whether in-hospital mortality rates among patients with serious conditions differ according to whether they are admitted on a weekend or on a weekday.
Morbidity and Mortality in Hypertensive Adults With a Low Ankle/Arm Blood Pressure Index
Authors: Anne B. Newman
Journal: JAMA (1993)

<h3>Objective.</h3> —To evaluate the relationship between the ankle/arm blood pressure index (AAI, the ratio of ankle to arm systolic blood pressure, a measure of peripheral arterial disease) and short-term cardiovascular morbidity and mortality in older adults with systolic hypertension. <h3>Design.</h3> —Prospective cohort study, 1- to 2-year follow-up (mean, 16 months). <h3>Setting.</h3> —Eleven of 16 field centers from the Systolic Hypertension in the Elderly Program. <h3>Participants.</h3> —1537 older men and women with systolic hypertension. <h3>Main Outcome Measures.</h3> —All-cause mortality, coronary heart disease (CHD) mortality, cardiovascular disease (CVD) mortality, and CHD and CVD morbidity and mortality. <h3>Results.</h3> —The AAI was measured at the 1989-1990 clinic examination and was 0.9 or less in 25.5% of 1537 participants. A low AAI was associated with most major CHD and CVD risk factors. In those with a low AAI (≤0.9) compared with those with an AAI of more than 0.9, age- and sex-adjusted relative risks for mortality end points at follow-up were as follows: total mortality, 3.8 (95% confidence interval [CI], 2.1 to 6.9); CHD mortality, 3.24 (95% CI, 1.4 to 7.5); and CVD mortality, 3.7 (95% CI, 1.8 to 7.7). For CVD morbidity and mortality, the age- and sex-adjusted relative risk was 2.5 (95% CI, 1.5 to 4.3). After adjustment for baseline CVD and other cardiovascular risk factors, the relative risk for total mortality was 4.1 (95% CI, 2.0 to 8.3) and for CVD morbidity and mortality, 2.4 (95% CI, 1.3 to 4.4). Results were similar when participants with clinical CVD at baseline were excluded. <h3>Conclusion.</h3> —A low AAI appears to be an important predictor of morbidity and mortality among older adults with systolic hypertension. (<i>JAMA</i>. 1993;270:487-489)
Prevention and Treatment of Traveler's Diarrhea
Authors: Alastair J.J. Wood, Herbert L. DuPont, Charles D. Ericsson
Journal: New England Journal of Medicine (1993)

More than 300 million people cross international boundaries each year1. Diarrhea is by far the most common medical problem among people traveling to the tropical and semitropical areas of Latin America; parts of the Caribbean, such as Haiti and the Dominican Republic; southern Asia; and North, East, and West Africa2. It affects 20 to 50 percent of such travelers3. The threat of diarrhea and the illness itself represent great economic costs to the traveling public and the host country. The loss of income from tourism and the failure of business ventures caused by the threat of illness . . .
Paying Physicians for High-Quality Care
Authors: Arnold M. Epstein, Thomas H. Lee, Mary Beth Hamel
Journal: New England Journal of Medicine (2004)

Payment incentives as a part of physicians' compensation are commonplace but have been aimed predominantly at restricting expensive services. A novel concept is the payment of physicians for providing high-quality care, on the basis of explicit measures of quality. Such a system has recently been adopted in the United Kingdom. The authors believe that the idea is worth pursuing, but they point out important impediments and challenges to its successful implementation.
Antifibrinolytic Treatment in Subarachnoid Hemorrhage
Authors: M. Vermeulen, K. W. Lindsay, G. D. Murray, F. Cheah, A. Hijdra, J. P. Muizelaar, M. Schannong, G. M. Teasdale, H. van Crevel, J. van Gijn
Journal: New England Journal of Medicine (1984)

We enrolled 479 patients with subarachnoid hemorrhage in a multicenter, randomized, double-blind, placebo-controlled trial to determine whether treatment with the antifibrinolytic agent tranexamic acid improves outcome by preventing rebleeding. At three months there was no statistical difference between the outcomes in the tranexamic acid group and the control group. Of the 173 patients who died, 84 had received tranexamic acid and 89 placebo (95 per cent confidence interval for the difference in mortality rate, -6 to 11 per cent). Similarly, when analysis was restricted to patients with an angiographically demonstrated aneurysm, there was no significant difference between the groups. This absence of effect was not due to a lack of antifibrinolytic action, since the rate of rebleeding was reduced from 24 per cent in the control group to 9 per cent in the tranexamic acid-treated group (chi-square = 18.07, P<0.001), but resulted from a concurrent increase in the incidence of ischemic complications (15 per cent in the control group and 24 per cent in the tranexamic acid group; chi-square = 8.07, P<0.01). We conclude that until some method can be found to minimize ischemic complications, tranexamic acid is of no benefit in patients with subarachnoid hemorrhage. (N Engl J Med 1984; 311:432–7.)
Circadian Rhythms: Mechanisms and Therapeutic Implications
Authors: Francis Levi, Ueli Schibler
Journal: The Annual Review of Pharmacology and Toxicology (2007)

The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cues in the synchronization of many, if not most, peripheral clocks, suggesting that the temporal coordination of metabolism and proliferation is a major task of the mammalian timing system. The inactivation of noxious food components by hepatic, intestinal, and renal detoxification systems is among the metabolic processes regulated in a circadian manner, with the understanding of the involved clock output pathways emerging. The rhythmic control of xenobiotic detoxification provides the molecular basis for the dosing time-dependence of drug toxicities and efficacy. This knowledge can in turn be used in improving or designing chronotherapeutics for the patients who suffer from many of the major human diseases.
Paracrine regulation of melanogenesis
Authors: X.H. Yuan, Z.H. Jin
Journal: British Journal of Dermatology (2017)

Melanocytes are generally characterized by the basic ability of melanin synthesis and transfer to adjacent keratinocytes. This constitutes an individual skin phenotype and provides epidermal protection from various stimuli, such as ultraviolet irradiation, through a complex process called melanogenesis, which can be regulated by autocrine or paracrine factors. Recent evidence has revealed the paracrine effects of keratinocytes on melanogenesis by secreting cytokines, including α‐melanocyte stimulating hormone and endothelin‐1. In addition to keratinocytes, there are other types of cells in the skin, such as fibroblasts and immune cells, which are also actively involved in the regulation of melanocyte behaviour through the production of paracrine factors. In addition, extracellular matrix proteins, which are secreted mainly by skin‐resident cells, not only play direct roles in regulating melanocyte morphology and functions but also provide structural support between the epidermis and dermis to control the distribution of various secreted cytokines from keratinocytes and/or fibroblasts, which are potentially involved in the regulation of melanogenesis. Moreover, understanding the origin of melanocytes (neural crest cells) and the presence of nerve endings in the epidermis can reveal the intimate contact between melanocytes and cutaneous specific nervous system proteins. Melanocytes are associated with all these networks with corresponding receptors expressed on the cell surface. In this review, we provide an overview of recent advances in determining the intimate relationships between melanocytes and their surrounding elements, which provide insights into the complex nature of the regulation of melanogenesis.
10. Cardiovascular Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2021</i>
Journal: Diabetes Care (2020)

The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.